JP3490658B2 - Whitening cosmetics - Google Patents

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a melanin production inhibitor and a whitening cosmetic composition, and more specifically, it is effective in improving skin color tone changes such as skin darkening, stains, freckles and the like due to exposure to ultraviolet rays, and safety. Highly effective melanin production inhibitor and whitening cosmetic. It also relates to an epidermal penetration barrier enhancer and a sebum secretion inhibitor.

[0002]

2. Description of the Prior Art When skin is exposed to ultraviolet rays, it has various effects. At that time, active oxygen, lipid peroxides and the like generated in the skin cause inflammation and seriously damage the skin tissue. These damages cause the skin to lose its moistness, texture and the like, and further have the effect on the dermis to form wrinkles, which causes photoaging. Also,
In addition to UV rays, many environmental factors (air pollution, stress,
It is also known that pigment cells (melanocytes) are activated by various factors released from peripheral cells by chemical or physical stimulation.

It is said that when melanocytes are activated, tyrosinase activity is increased and melanin is excessively produced and transferred to epidermal cells, resulting in a change in skin color tone and blackening.

[0004] As such factors released from peripheral cells, endothelin-1 released from epidermal cells, melanocyte stimulating hormone and the like are known. In addition, histamine was reported to be released from mast cells with UV irradiation (1981 Gilcherest BA, et al. JOU).
RNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
5: 411-422). In recent years, it has been revealed that histamine and nitric oxide released from mast cells also have a similar melanocyte stimulating action.

Therefore, in order to exhibit a whitening effect, it is important not only to suppress the activity of tyrosinase and suppress the production of melanin, but also to suppress the stimulation of melanocytes caused by exposure to ultraviolet rays and environmental factors. Further, no effective means for preventing or treating hyperpigmentation such as sickle egg spots or sequelae of inflammation has been found so far.

Further, in order to minimize the damage to the skin, it is considered that the epidermal permeation barrier function which the skin naturally has is enhanced. The epidermal permeation barrier function is a function of epidermal tissue that prevents entry of substances into a living body, mitigation of stimulus transmission, and excessive evaporation of water from inside the living body. As described above, this function is temporarily disrupted by many environmental factors other than ultraviolet rays and disturbs the skin internal environment. In such a state, the external stimulus acts more directly on the skin tissue and the damage to the skin becomes stronger. The state in which the epidermal permeation barrier is disintegrated is that the skin surface is dry and the scales cover the surface, which is also cosmetically unfavorable, and it needs to be promptly repaired, and the epidermal permeation barrier function is enhanced and disintegrated. It is important to make it difficult.

In order to obtain beautiful white skin, it is important to deal with sebum in addition to the problems mentioned above. In recent years, sebum tends to be excessively synthesized due to abnormal endocrine system (sex hormone) balance due to westernization of diet and stress. Excessive secretion of sebum makes it easier to block pores that are openings to the skin surface of the sebaceous glands with dust in the air, etc., and not only does the skin look dark or dull, but it is also easy to cause comedoes, etc. May cause inflammation due to bacteria. Excessive secretion of sebum causes cosmetic deterioration such as shiny skin and foundation caused by makeup, which is not desirable in terms of beauty. Therefore, it is preferable to suppress sebum secretion.

Conventionally, kojic acid, arbutin, in order to prevent darkening of the skin, stains and freckles, and maintain the original white skin,
Whitening cosmetics containing hydroquinone monobenzyl ether, hydrogen peroxide, etc. have been proposed.

Addition of arbutin, kojic acid, hydroquinone monobenzyl ether, etc., has the effect of lightening slightly dark skin, but not at the desired level. In addition, there is no action to alleviate damage to the skin caused by ultraviolet rays and the like, and there are cases in which there is a problem in terms of skin safety.

Further, no whitening cosmetic composition having the above-mentioned effects of strengthening the epidermal permeation barrier and suppressing sebum secretion has been provided at all.

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to effectively improve changes in skin tone such as dark skin, stains and freckles caused by exposure to ultraviolet rays, and a highly safe melanin production inhibitor and whitening makeup. To provide the fee. In addition, it strengthens the epidermal permeability barrier function against the influence from the environment, rapidly improves the disintegration of the epidermal permeation barrier, and has an excellent effect of keeping cosmetically healthy skin. The present invention relates to a sebum secretion inhibitor that can suppress skin irritation, and to provide a whitening cosmetic that also has the function.

That is, the present invention has an effect of suppressing sebaceous gland activity for preventing the formation and development of comedo, an effect of enhancing the function of the epidermal permeation barrier, and an effect of rapidly improving the collapse of the epidermal permeation barrier, and an effect of suppressing melanin production. , Excellent whitening effect, high stability in the formulation, and high skin safety,
It is an object of the present invention to provide a whitening cosmetic composition which has an excellent effect of keeping skin healthy cosmetically.

[0013]

[Means for Solving the Problems] In view of such a situation, the inventors of the present invention have conducted diligent research to improve the difficulties of the prior art, and as a result, a specific chroman derivative suppresses sebaceous secretion. It was found that they have an inhibitory effect and an effect of enhancing the epidermal permeation barrier function, a markedly superior effect of suppressing melanin production, and an effect of suppressing the release of stimulating factors from melanocyte peripheral cells. Further, it was also found that the chroman derivative according to the present invention serves as a whitening cosmetic for the purpose of preventing and treating spots, freckles, and dark skin tones caused by sunburn, and thus the present invention has been completed.

That is, the present invention contains a melanin production inhibitor, an epidermal permeation barrier enhancer, a sebum secretion inhibitor and the derivative thereof, which contains the chroman derivative represented by the general formula (I) and / or (II) as an active ingredient. About whitening cosmetics.

[0015]

[Chemical 9]

[0016]

[Chemical 10]

[0017]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described in detail below.

The chroman derivative used in the whitening cosmetic composition of the present invention is a known substance (US Pat. No. 5,605,703).
issue). However, it is not known at all to have the effect of improving the epidermal permeation barrier of the present invention, the effect of suppressing sebum secretion, the effect of suppressing melanin production, and the effect of suppressing the release of a stimulating factor from melanocyte pericytes, and no analogy was possible. .

The melanin production inhibitor, epidermal permeation barrier enhancer and sebum secretion inhibitor according to the present invention are used as a single active ingredient, and in addition to cosmetics and other compositions for external use on the skin, pharmaceuticals, and pharmaceutical departments. It can be mixed with external products.

The amount of the chroman derivative represented by the general formula (I) and / or (II) in the whitening cosmetic composition of the present invention is preferably 0.001-5.
0 mass% (hereinafter referred to as%) is preferable. 0.001%
If it is less than the above range, the desired effect of the present invention may not be sufficient, and even if the compounding amount exceeds 5.0%, it may not be possible to expect an improvement in the effect commensurate with the increase, and the feel during use may be poor. It may become worse and it may be difficult to hold the individual dosage form.

The whitening cosmetic composition of the present invention may be used not only as a cosmetic composition which is generally applied to the skin but also as a bath agent. As the dosage form, it is considered that generally used aqueous solution, W / O type or O / W type emulsion, granules and other powders, tablets and the like by using a suitable vaginal form, etc. Examples include creams, emulsions, lotions, packs, gels, sticks, sheets, paps and the like. In the case of an emulsion or the like, this whitening cosmetic can be produced by a usual method of heating and dissolving an oil phase and an aqueous phase, emulsifying and dispersing, and cooling.

In the cosmetic of the present invention, in addition to the above raw materials, tar-based pigments, coloring pigments such as iron oxide, preservatives such as parabens, fatty acid soaps, anionic surfactants such as sodium cetyl sulfate, Nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene polyhydric alcohol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyhydric alcohol fatty acid ester, polyglycerin fatty acid ester, tetraalkylammonium Cationic surfactants such as salts, betaine-type, sulfobetaine-type, sulfoamino acid-type, amphoteric surfactants such as sodium N-stearoyl-L-glutamate, natural interfaces such as lecithin and lysophosphatidylcholine Activator, 1,3-butylene glycol, dipropyi Glycol, polyethylene glycol, polyhydric alcohols such as glycerin, saccharides such as sorbitol, maltitol, gelatin, casein, starch, gum arabic, karaya gum, guar gum, locust bean gum, dragacant gum, quince seed, pectin, color ginnan, sodium alginate, etc. Natural polymers of, methyl cellulose, hydroxyethyl cellulose,
Semi-synthetic polymers such as hydroxypropyl cellulose, sodium carboxymethyl cellulose, ethyl cellulose, polyvinyl alcohol, polyvinyl methyl ether and copolymer, polyvinylpyrrolidone, sodium polyacrylate, carboxyvinyl polymer, synthetic polymers such as polyethylene oxide polymer, xanthene gum, etc. The thickener, the pigment such as titanium oxide, the antioxidant such as dibutylhydroxytoluene, and the like can be appropriately added within a range that does not impair the object of the present invention.

[0023]

EXAMPLES The present invention will be described in detail below based on Examples, Comparative Examples and Production Examples. The present invention is not limited to these. The chroman derivative (II) used in the following tests, examples and the like has the above general formula (II) in which R ₃ is CH ₃ O— and R ₄ is HO—.
Hereinafter, this is abbreviated as Chroman (II).

Examples 1 to 3 and Comparative Example 1

(1) Melanin production inhibition test B16 melanoma cells (3 × 10 ⁵ cells) were seeded on a φ90 mm plastic petri dish, and a sample ethanol solution was added to a final ethanol concentration of 10% FBS.
-Culturing was performed in 10 mL of DMEM medium at 37 ° C in a 5% CO ₂ atmosphere for 72 hours. After the completion of the culture, the cells were washed with PBS, detached with trypsin-EDTA and centrifuged to collect the cells. The obtained cells were treated with 5% TCA, ethanol-ether = 3: 1, ether. Further, it is dissolved with Solen 350, and a wavelength of 40 is obtained using a spectrophotometer.
Absorbance was measured at 0 nm. On the other hand, the inhibition rate (%) was determined by setting the absorbance of 100 to which only ethanol was added instead of the sample solution.

(2) Histamine release inhibition test After Wistar rats (8 weeks old) were exsanguinated and killed,
25 mL of 0.1% (w / v%) bovine serum albumin (B
The peritoneal cells were obtained by washing the abdominal cavity with phosphate buffered saline (PBS) containing SA). The collected cells are washed with PBS containing BSA, and centrifuged at 4 ° C. for 40 G for 5 times.
Perform for minutes to collect cells. The collected cells are again suspended in PBS containing BSA and adjusted to a concentration containing 5 × 10 ⁵ / mL mast cells. Samples from 1.0 to 100 mg / mL
Dissolved in ethanol at the concentration of 1 μL of BSA-containing PB
After adding to S799 μL and keeping at 37 ° C. for 5 minutes, 100 μL of the above cell suspension was added, and after incubation at 37 ° C. for 15 minutes, 100 μL of a substance P solution of 30 μmol / L was added and further 10 Incubate at 37 ° C for minutes.
Ice-cooled PB containing 0.1% BSA and 1% glucose
Add 1 mL of S to stop the reaction. The reaction solution was centrifuged for 5 minutes and separated into supernatant and sludge, and the amount of histamine in each was determined by the method of Shore et al. (1959 JOURNAL OF PHA
RMACOLOGY AND EXPERIMENTAL THERAPEUTICS 127
Volume 182 to 186) by fluorescence measurement,
The inhibition rate (%) was determined by setting the histamine release amount without addition of substance P as 100, and defined as the inhibition rate.

[0027] [Table 1]                                         Melanin production Histamine release                               Concentration suppression test Suppression test             Compound name (%) Inhibition rate (%) Inhibition rate (%) Example 1 Chroman (II) 0.01 Not performed 76.5 Example 2 Chroman (II) 0.001 85.0 32.3 Example 3 Chroman (II) 0.0001 39.2 20.3 Comparative Example 1 --- 0 0

The results of various tests are shown in Table 1.
As shown in Table 1, Examples 1 to 3 had a remarkable melanin production suppressing effect and histamine release suppressing effect as compared with Comparative Example 1. And the suppressing effect was concentration-dependent.
In addition, by further examining the mechanism of action of suppressing melanin production, metallothionein, which is an antioxidant produced in cells and acts as a scavenger of free radicals generated during inflammation, increases resistance to external stimuli. It was found to induce production. That is, it has been revealed that it has an inhibitory effect on tyrosinase activity of melanocytes, which is increased by stimulation of nitric oxide, endothelin, α-MSH and the like by inducing melanocyte metallothionein production, and eventually shows inhibition of melanin production.

Example 4, Comparative Example 2 (3) Colored Guinea Pig UV Pigment Deposition Inhibition Test The minimum erythema dose of UVB region ultraviolet light was applied to one location on the back skin of 10 hair-removed A1 type guinea pigs (6 weeks old, female) ( 2c
m × 2 cm) was continuously irradiated for 3 days. Immediately after irradiation, the sample (ethanol solution of each concentration) was applied twice a day for 3 weeks, and after 3 weeks, DOPA was used as an index for pigmentation of this site.
The number of positive cells was counted and used as the evaluation result.

[Table 2] Compound name Concentration UV pigmentation inhibition (%) Test result Number / mm ² Example 4 Chroman (II) 1.0 512 ± 10 Comparative Example 2 −−675 ± 10 P <0.001, Mean ± standard error

The results of the color guinea pig UV pigmentation inhibition test are shown in Table 2. Example 4 showed an excellent inhibitory effect on pigmentation by UVB.

Example 5 and Comparative Example 3 (4) Epidermal permeation barrier improvement test Transepidermal water loss (hereinafter abbreviated as TEWL) was measured by a continuous sweating measuring device Hydrograph AMU-100 (manufactured by K & S Co.). The measurement was performed as follows. 1 square centimeter capsules on hairless mouse back skin (10
The water vapor amount in the nitrogen gas was measured before adsorbing the nitrogen gas into the capsule (300 ml / min) and collecting the nitrogen gas into the capsule, after adhering to 5 weeks old (1 group, 5 animals). From the difference in this value, the amount of water (milligram) evaporated from one square centimeter of skin per minute was calculated and defined as TEWL.

Samples were prepared by mixing Chroman (II) with an aqueous solution (base) of 0.5% polyoxyethylene nonylphenyl ether (NP-15; manufactured by Nikko Chemicals Co., Ltd.) as shown in Table 3. First, 0.05 mL of this sample was applied to the skin (diameter of about 2.5 cm) whose TEWL was measured in advance once a day.
Once, 5 times a week for continuous application for 1 week (pre-application). Then, on the third day after the final application of the preliminary application, the ultraviolet B wavelength (UVB) was irradiated once at 0.15 J / cm ² . Then, the TEWL on the 4th day after irradiation is measured,
TE by UVB based on TEWL at the start of the test
TEWL which is a relative value indicating how much WL has changed
The variation rate was calculated and the average value of each group was compared with the base group.

TEWL fluctuation rate = TEWL 4 days after irradiation
/ TEWL at the start of the test

[0035] [Table 3]               Compound name Concentration TEWL fluctuation rate                             (%) (4th day) Example 5 Chroman (II) 0.1 6.8 ± 1.4 Comparative Example 3 --11.6 ± 1.1                             P <0.05, mean ± standard error

The results are shown in Table 3. As shown in Table 3,
In Example 5, as compared with Comparative Example 3, the collapse of the epidermal permeation barrier due to UVB was clearly smaller and the epidermal permeation barrier was strengthened.

Example 6, Comparative Examples 4 to 5 (5) Sebaceous Gland Diameter Inhibition Test 0.1% of the test compound was dissolved in ethanol (base) to prepare samples. Then, as a control, only the base and 0.02% of retinoic acid (all-trans, manufactured by Sigma), which is known as a remedy for acne, were used. Each sample 0.
05 mL of rhinomouse dorsal skin (18 weeks old, 1 group 4
The animals were applied once a day and 5 times a week for 3 consecutive weeks. Then, the mice were sacrificed 3 days after the final application of the sample, and the dorsal skin was collected (2 × 4 cm). This skin was immersed in a 0.5% acetic acid aqueous solution for 18 hours (4 ° C.) to peel off the epidermis. Then, it was attached to a slide glass with the skin side facing down, dehydrated with alcohol / xylene system, and enclosed with balsam. A photograph was taken under a microscope (25 times) for 5 fields of view for each specimen, and the diameter (average value of major axis and minor axis) of 10 sebaceous glands in one field was measured with a caliper. This diameter indicates the size of the sebaceous gland, and when the activity of the sebaceous gland is active, the sebum accumulated in the sebaceous gland increases and the diameter increases. Conversely, when the activity of the sebaceous gland is suppressed, the accumulated sebum decreases. The diameter becomes smaller. Also,
The values are shown as values converted using a micrometer taken at the same magnification. The results are shown in Table 4.

[0038] [Table 4]             Compound name Concentration Sebaceous gland diameter                           (%) (Μm) Example 6 Chroman (II) 0.1 112.25 ± 0.84 Comparative Example 4--125.70 ± 3.26 Comparative Example 5 Retinoic acid 0.02 64.26 ± 0.59                 In addition, in Example 6 and Comparative Example 4, P <0.001, average value ± standard error

From the results of this test, it is apparent that in Example 6, the sebaceous gland diameter was clearly smaller than that in Comparative Example 4. On the other hand, comparing Example 6 with Comparative Example 5, it can be seen that Comparative Example 5 is more effective. However, in the visual observation of the skin surface, no abnormality was observed on the skin surface in Example 6 at all, but in Comparative Example 5, erythema which seems to be an inflammatory state was observed along with a large amount of desquamation, and a rough skin state was observed. It was When the transepidermal water loss, which is an index of the rough skin condition, was measured, a very high value of ² mg / cm ² / min was observed (normal value and 0.06 mg / cm ^{2 in} Example 6).
/(Min./min. Or less), it was found that the skin was in a state of severe rough skin. Therefore, it was found that the present invention can suppress the activity of the sebaceous glands without seriously affecting the skin.

In the following, it was investigated whether the substance can be used in a widely used dosage form.

Example 7 (Skin lotion for whitening) A skin lotion having the composition shown in Table 5 was prepared by the following preparation method.

Preparation Method After uniformly dissolving the B component shown in Table 5 below in the A component,
The components A and C are uniformly mixed, stirred, dispersed, and then filled in a container.

[0043] [Table 5]     Raw material ingredients Amount (%) (A)   ・ Ethanol 10.0   ・ Polyoxyethylene monolaurate (20) 5.0         Sorbitan   ・ Dibutylhydroxytoluene 0.01   ・ Perfume 0.05 (B)   ・ Chroman (II) 0.1 (C)   ・ Glycerin 5.0   ・ Xanthan gum 0.1   ・ Hydroxyethyl cellulose 0.1   ・ Remaining amount of purified water

The skin lotion of Example 7 was very stable even as a preparation, and did not cause skin irritation even when continuously applied to humans, and had high safety. The same was true for other chroman derivatives.

Example 8 (Skin Cream) A skin cream having the composition shown in Table 6 was prepared by the following preparation method.

Preparation Method The mixture of the component B and the component A described below and the component C are uniformly heated and dissolved to bring the temperature to 80 ° C. Then, after injecting the component C into the component A and emulsifying it, the mixture is cooled to 30 ° C. with stirring.

[0047] [Table 6]     Raw material ingredients Amount (%) (A)   ・ Glycerin monostearate 2.0   ・ Beeswax 1.0   ・ Polyoxyethylene (6) sorbitan 1.0           Monooleate   ・ Vaseline 4.0   ・ Liquid paraffin 12.0 (B)   ・ Chroman (II) 1.0   * 1,3-butylene glycol 5.0 (C)   -N-stearoyl-L-glutamic acid Na 1.0   ・ Carrageenan 0.3   ・ Methylparaben 0.1   ・ Remaining amount of purified water

The skin cream of Example 8 was very stable even as a preparation, and did not cause skin irritation even when continuously applied to humans, and had high safety. The same was true for other chroman derivatives.

Examples 9 and 10 (beauty essence) A beauty essence was prepared by the following preparation method and composition.

Preparation method: Component A and component B are uniformly dissolved and dispersed, and then component A and component B are mixed and stirred, dispersed, and then filled in a container.

[0051]     Raw material ingredients Amount (%)                                             Example 9 Example 10 (A)   ・ 1,3-Butylene glycol 55   ・ Dipropylene glycol 05   ・ Ethanol 05   ・ Chroman (II) 0.1 0.5   ・ Raffinose 11   ・ Polyoxyethylene hydrogenated castor oil (80) 0.1 0.1   ・ Fragrance 0.02 0.02 (B)   ・ Phenoxyethanol 0.2 0.2   ・ Pectin 0 0.05   ・ Xanthan gum 0.05 0.1   ・ Sodium hyaluronate 0.05 0   ・ Carrageenan 0 0.1   ・ B16 polymer (Note A) 0.05 0.01   ・ Sodium citrate 0.05 0.1   ・ Horsetail extract 0.1 0.1   ・ Diisopropylamine dichloroacetic acid 0.2 0.2   -Γ-amino-β-hydroxybutyric acid 0.2 0.2   ・ Dipotassium glycyrrhizinate 0.2 1   ・ Decarboxycarnosine hydrochloride 0.05 0.05   ・ Hibiscus extract 0.2 0.5   ・ Carrot extract 0.1 1.0   ・ Lactic acid bacterium culture solution 0.1 0.1   ・ Remaining amount of purified water Note A: Microorganism (Alkaline Genes Latas B-16 strain, deposit number FERM BP -2015) produced polysaccharides

Examples 11 and 12 (O / W type cream) O / W type creams were prepared by the following preparation methods and compositions.

Preparation method A mixture of the component B with the component A and the component C are uniformly heated and dissolved to bring the temperature to 80 ° C. Then C
After injecting the component A into the component and emulsifying it, 30 with stirring
Cool to ° C.

[0054]     Raw material ingredients Amount (%)                                             Example 11 Example 12 (A)   ・ Stearic acid 11   ・ Isostearic acid 0 1   ・ Glycerin monostearate 2 2   ・ Behenyl alcohol 2 2   ・ White beeswax 1 1   ・ Cetyl myristate 11   ・ Sorbitan sesquioleate 11   * N-stearoyl phytosphingosine 0.1 0.1   ・ Hydrogenated lecithin 0.1 0.1   ・ Plant squalane 5 5   ・ Octyldodecyl myristate 55 (B)   * 1,3-butylene glycol 510   ・ Chroman (II) 0.2 1 (C)   ・ Fire thorn extract 0.1 0.3   ・ Water-soluble licorice extract 0 0.1   ・ Urea 0 0.5   ・ Concentrated glycerin 55   ・ Paraoxybenzoic acid ester 0.2 0.2   -N-acetylglucosamine oligomer 0.1 0.1   ・ Ascorbic acid glucoside 0.2 0.2   ・ Γ-Aminobutyric acid 0.1 0.1   -Sodium N-stearoyl glutamate 0.2 0.2   ・ Alkyl-modified carboxyvinyl polymer 0.1 0.2   ・ B16 polymer (Note A) 0.05 0.01   ・ Tea fruit extract 0.001 0.1   ・ Nicotinamide 0.1 0.1   ・ Sarcosin 0.1 0.1   ・ Remaining amount of purified water Note A: Microorganism (Alkaline Genes Latas B-16 strain, deposit number FERM BP -2015) produced polysaccharides

Examples 13 to 15 (O / W type emulsion) An O / W emulsion was prepared by the following preparation method and composition.

Preparation method A mixture of the component B with the component A and the component C are uniformly heated and dissolved to bring the temperature to 80 ° C. Next, inject A component into C component and emulsify it, then at 30 ° C with stirring.
Cool down.

[0057]     Raw material ingredients Amount (%)                                       Example 13 Example 14 Example 15 (A) ・ Decamethylcyclopentasiloxane 10 10 10 ・ Isostearyl isostearate 100 ・ Olive oil 0 10 ・ Macadamia nut oil 0 0 1 ・ Eucalyptus oil 0.1 0 0.1 ・ Hexyldecanol 1 0.1 0 -Dl-alpha tocopherol nicotinate 0 0.10 ・ Polyoxyethylene hydrogenated castor oil (60) 2 2 2 2 ・ Spherical silicone powder (Note 1) 1 1 5 (B) * 1,3-butylene glycol 5 10 10 ・ Chroman (II) 0.02 0.2 2 (C) ・ Water-soluble chlorophyll 0.02 0.05 0.02 ・ Salvia extract 0 0.3 0.1 ・ Sorbitol liquid 3 3 3 ・ Polyethylene glycol 4000 125 ・ Carboxyvinyl polymer 0.2 0.2 0.1 ・ Xanthan gum 0 0.1 ・ Sugar ceramide (Note 2) 0.1 0.1 0.1 ・ Paraoxybenzoic acid ester 0.2 0.2 0.2 ・ Geo extract 0.01 0.1 1.0 ・ Mevalonolactone 0.5 0.5 0.5 0.5 ・ Edetate 0.02 0.02 0.02 ・ Potassium hydroxide 0.05 0.05 0.02 ・ Purified water Remaining amount Remaining amount Remaining amount Note 1; Toshiba Silicone Tospearl 2000B * Note 2: Biobunceramide manufactured by Kibun Food Chemical Co., Ltd.

Examples 16 to 18 (W / O type emulsion) A W / O type emulsion was prepared by the following preparation method and composition.

Preparation method A mixture of the component B with the component A and the component C are uniformly heated and dissolved to bring the temperature to 80 ° C. Next, inject C component into A component and emulsify it, then at 30 ° C with stirring.
Cool down.

[0060]     Raw material ingredients Amount (%)                                     Example 16 Example 17 Example 18 (A) ・ Co-modified silicone (Note 3) 220 ・ Polyoxyethylene modified 0 2 2           Silicon dispersion (Note 4) ・ Sorbitan monoisostearate 002 ・ Squalane 0 0 10 ・ Decamethylcyclopentasiloxane 15 20 10 ・ Methylpolysiloxane 5 2 3 ・ Long-chain branched fatty acid cholesteryl (Note 5) 0 0 3 ・ Silicone elastomer dispersion (Note 6) 5 2 1 (B) * 1,3-butylene glycol 5 510 ・ Chroman (II) 0.05 0.1 0.5 (C) ・ Licorice extract 0.1 0.1 0.1 ・ Water-soluble chlorophyll 0.02 0.05 0.05 ・ Sodium chloride 1 1 1 ・ Concentrated glycerin 5 5 5 ・ Raffinose 1 1 1 1 ・ Paraoxybenzoic acid ester 0.3 0.3 0.3 -N-methyl-L-serine 0.5 0.5 0.5 ・ Tsubaki seed extract 0.001 0.01 0.1 ・ Purified water Remaining amount Remaining amount Remaining amount Note 3; ABIL EM90 manufactured by Gold Schmidt Note 4: BY22-008 manufactured by Toray Dow Corning Silicone Co., Ltd. Note 5: YOFCO CLE-NH manufactured by Nippon Seika. * 6: Toray Dow Corning Silicone Trefil E-507       (Only Example 18 uses Trefil E-508)

Examples 19-21 (Sunscreen) A sunscreen was prepared by the following preparation method and composition.

Preparation method The mixture of component B and component A described below and component C are uniformly heated and dissolved to bring the temperature to 80 ° C. Then, after injecting the component C into the component A and emulsifying it, the mixture is cooled to 30 ° C. with stirring.

[0063]     Raw material ingredients Amount (%)                               Example 19 Example 20 Example 21 (A)   ・ Dioctyl ether 22 15 10   ・ Co-modified silicone (Note 7) 2 2 2   ・ Mono-isostearic acid 0 2       Sorbitan   ・ Tri-2-ethylhexanoic acid 0 0 5       Glyceryl   ・ Hardened oil 0 0 0.1   ・ Methylphenyl polysiloxane 0 30   ・ Macadamia nut fatty acid 0 0 2       Phytostearyl   ・ Paramethoxycinnamic acid 0 7 7       2-ethylhexyl   ・ Titanium oxide 504   ・ Zinc oxide 504 (B)   * 1,3-butylene glycol 10 10 10   ・ Chroman (II) 0.01 0.1 1   ・ Licorice flavonoid 0.01 0.001 0.1 (C)   ・ Magnesium chloride 1 1 1   ・ Glycine 0.1 0.1 0.1   ・ Phenoxyethanol 0.3 0.3 0.3   ・ Hibiscus extract 1 1 1 1   ・ Aloe extract 0.1 0.1 0.1   ・ Purified water Remaining amount Remaining amount Remaining amount Note 7: Gold Schmidt ABIL EM90

[0064]

INDUSTRIAL APPLICABILITY As described above, the present invention has an effect of inhibiting sebaceous gland activity that prevents the formation and development of comedo, an effect of enhancing the epidermal permeability barrier function, and an effect of rapidly improving the collapse of the epidermal permeability barrier. is doing. Further, it provides a highly safe whitening cosmetic that is effective in improving the change in skin tone such as dark skin, stains, freckles, and dullness due to exposure to ultraviolet rays, and has the effect of suppressing the release of stimulating factors from the cells surrounding melanocytes. To do. Further, it is possible to provide a whitening cosmetic which is excellent in safety and has stable formulation, such as no skin irritation.

─────────────────────────────────────────────────── ─── Continued Front Page (51) Int.Cl. ⁷ Identification FI A61K 31/353 A61K 31/353 // A61P 17/00 A61P 17/00 C07D 311/70 C07D 311/70 311/72 311/72 (58) Fields surveyed (Int.Cl. ⁷ , DB name) A61K ⁷ /00-7/50 A61K 31/352-31/355 CA (STN) CAOLD (STN)

Claims (4)

(57) [Claims] 1. A whitening cosmetic containing a chroman derivative represented by the general formula (I) and / or (II). [Chemical 1] [Chemical 2] 2. A melanin production inhibitor containing a chroman derivative represented by the general formula (I) and / or (II) as an active ingredient. [Chemical 3] [Chemical 4] 3. A skin permeation barrier enhancer containing a chroman derivative represented by the general formula (I) and / or (II) as an active ingredient. [Chemical 5] [Chemical 6] 4. A sebum secretion inhibitor comprising a chroman derivative represented by the general formula (I) and / or (II) as an active ingredient. [Chemical 7] [Chemical 8]